The Transfusion Safety Study (TSS) is a multifaceted cooperative contract program, sponsored by the National Heart, Lung, and Blood Institute, to evaluate factors influencing the risk of transfusion-transmitted human immunodeficiency virus (HIV) infection and its progression to clinically significant manifestation. Participating clinical centers and blood services are located in four cities: New York, Miami, San Francisco, and Los Angeles. The coordinating center and central laboratories are located in Los Angeles and Seattle. Subjects include: l) persons in the four highest prevalence areas of the United States who donated blood from September, 1984 through January, 1985, just before routine donor screening was begun; 2) recipients of components form ant-HIV-positive and anti-HIV-negative donors; 3) patients with congenital bleeding disorders receiving concentrates and components; 4) patients with congenital anemias receiving large numbers of transfusions; 5) untransfused subjects; 6) household contracts of patients wit bleeding disorders or anemias; 7) recipients of components from anti-HTLV-I- positive and negative components. The TSS is a unique study of the major aspects of transfusion medicine and AIDS. There are many aspects and activities in TSS, begun under the aegis of the original contract investigation, that require longer follow- up.